Estimating the risk of recurrent invasive pneumococcal disease in Australia, 1991-2016.

BACKGROUND: Individuals who experience an initial episode of invasive pneumococcal disease (IPD) are at increased risk of recurrent episodes. However, the magnitude of risk has not been well-quantified in the pneumococcal conjugate vaccine era. Individuals with a previous episode of IPD are not commonly identified as a high-risk group in vaccination guidelines. METHODS: Australian residents with at least one case of IPD between 1991 and 2016 were identified using routine public health surveillance data which included identified IPD risk factors. Incidence of recurrent IPD was calculated from 2001 onwards (after IPD became nationally notifiable) using time-to-event analyses with individuals contributing person-time at risk of recurrence if they survived greater than 14 days after initial episode onset. RESULTS: From 1991 to 2016 there were 28,809 IPD episodes in 28,218 individuals. A total of 512 (1.8%) persons experienced 591 recurrent episodes. From 2001 to 2016 the incidence of recurrent IPD was 216.2 per 100,000 person-years, 27 times greater than the population rate of primary IPD during this period (8.0 per 100,000 population per year). Between 2011 and 2016, more than one-quarter of individuals experiencing recurrence had no IPD risk factors identified at first episode. CONCLUSIONS: There is substantially increased risk of recurrent IPD after an initial episode. At least one-quarter of those with recurrent episodes have no identified risk factors at the initial episode. Given the potential preventability of future episodes, those with a previous IPD episode should be identified as a high-risk group and receive pneumococcal vaccination.

Evidence for an increase in the intensity of inter-seasonal influenza, Queensland, Australia, 2009-2019.

BACKGROUND: Inter-seasonal influenza cases have been increasing in Australia. Studies of influenza seasonality typically focus on seasonal transmission in temperate regions, leaving our understanding of inter-seasonal epidemiology limited. We aimed to improve understanding of influenza epidemiology during inter-seasonal periods across climate zones, and explored influenza intensity and strain dominance patterns over time. METHODS: Queensland state-wide laboratory-confirmed influenza notifications and public laboratory influenza test data from 2009-2019 were described by demographics, time period, region and strain type. We compared influenza intensity over time using the WHO Average Curve method to provide thresholds for seasonal and inter-seasonal periods. RESULTS: Among the 243 830 influenza notifications and 490 772 laboratory tests reported in Queensland between 2009 and 2019, 15% of notifications and 40% of tests occurred during inter-seasonal periods, with 6.3% of inter-seasonal tests positive. Inter-seasonal notifications and tests substantially increased over time and increases in weekly proportions positive and intensity classifications suggested gradual increases in virus activity. Tropical inter-seasonal activity was higher with periods of marked increase. Influenza A was dominant, although influenza B represented up to 72% and 42% of notifications during some seasonal and inter-seasonal periods, respectively. CONCLUSIONS: Using notification and testing data, we have demonstrated a gradual increase in inter-seasonal influenza over time. Our findings suggest this increase results from an interplay between testing, activity and intensity, and strain circulation. Seasonal intensity and strain circulation appeared to modify subsequent period intensity. Routine year-round surveillance data would provide a better understanding of influenza epidemiology during this infrequently studied inter-seasonal time period.

Effectiveness of quadrivalent influenza vaccination in the first year of a funded childhood program in Queensland, Australia, 2018.

BACKGROUND: Following high influenza activity in 2017, the state of Queensland, Australia, funded a quadrivalent inactivated influenza vaccination program for children aged 6 months to <5 years in 2018. We calculated influenza vaccine effectiveness (VE) among children eligible for this program. METHODS: A matched case-control study was conducted. Cases were identified using Queensland 2018 influenza notification data among children age-eligible for funded vaccination. Controls were drawn from Australian Immunisation Register records of Queensland resident children age-eligible for funded influenza vaccine. Up to 10 controls per case were matched for location and birthdate. First dose vaccination was valid if received ≥14 days prior to specimen collection; a second dose was valid if received ≥28 days after first dose receipt. VE was calculated for vaccine doses and adherence to national recommendations for two doses in the first season (schedule completeness) and adjusted (VEadj) for sex and First Nations status. RESULTS: There were 1,125 cases and 10,645 matched controls analysed. Overall VEadj against laboratory-confirmed influenza was 51% (95% confidence interval (CI) 41-60). VEadj was 60% (95% CI 46-70) for children who received two doses in 2018, and 60% (95% CI 48-69) for children vaccinated appropriately according to schedule completeness. VE increased with age. CONCLUSIONS: Moderate vaccine effectiveness was observed for children eligible for the funded program in Queensland in 2018, adding to the sparse evidence for influenza vaccine use in Australian children. Adhering to the national first season two dose schedule for influenza vaccine receipt in children ensures maximum protection.

Genomic Characterization of Recent and Historic Meningococcal Serogroup E Invasive Disease in Australia: A Case Series.

We report the recent emergence of invasive meningococcal disease due to serogroup E in Queensland, Australia, in previously healthy patients. Molecular typing revealed the genotype of these strains to be E:P1.21-7,16:F5-36:ST-1157 (cc1157); when analyzed phylogenetically, compared with international cc1157 strains, they were relatively unrelated to each other.

Perinatal immunoprophylaxis in babies born to hepatitis B virus-positive mothers in Queensland Australia: A data linkage study.

Vertical transmission from mother-to-child is an important mode of hepatitis B virus (HBV) infection, accounting for up to half of all incident cases globally. We evaluated the uptake of HBV neonatal vaccination and immunoglobulin delivery in Queensland, Australia, between 2001 and 2013. We identified HBV-positive mothers using linked notifiable conditions, hospitalisation, and perinatal administrative data. Perinatal receipt of monovalent HBV vaccine and hepatitis B immunoglobulin were examined. Of 710,859 live births, with 5753 infants (0.81%) born to identified HBV-positive mothers; 91.7% received HBV neonatal vaccine. Immunoglobulin uptake was 20.0% in 2012 and 36.6% in 2013. Uptake was higher when the mother's HBV-positive status was recorded in perinatal records (69.6% if maternal HBV status recorded on perinatal data collection vs 9.5% otherwise). Delivery of neonatal HBV vaccination in Queensland was high. Improved identification and documentation of HBV-positive mothers' status during the antenatal period was associated with increased immunoglobulin administration.

An outbreak of Q fever associated with parturient cat exposure at an animal refuge and veterinary clinic in southeast Queensland.

OBJECTIVE: To determine the source of a Q fever outbreak in humans at an animal refuge and veterinary clinic in southeast Queensland from October to December 2016. METHODS: Case interviews and a retrospective cohort study of animal refuge and veterinary clinic staff using a self-administered questionnaire related to clinical history of Q fever, Q fever vaccination status and workplace activities during the exposure period. RESULTS: Seven cases (six confirmed, one probable) were identified. Forty-three questionnaires were completed (92% response rate). Workplace activities associated with the greatest risk of illness were the disposal of deceased cats or dogs (RR, 14.0; 95%CI, 1.9-104.1) and participating in euthanasia of cats or dogs (RR, 4.6; 95%CI, 1.3-16.9). Five feline birthing events occurred at the animal refuge from 25 September to 19 October 2016, each with subsequent euthanasia of the queen cat and litter. All cases had likely exposure to a specific queen cat and her litter that were euthanised the same day as the birthing event. CONCLUSIONS: A parturient cat was the most likely source of the outbreak. Implications for public health: Occupational groups and others with regular exposure to feline or canine parturient products should receive Q fever vaccine.

Screening for diabetes prevention with diabetes risk scores - A balancing act.

AIMS: To compare the diabetes prevention impact and cost of several screening scenarios for diabetes prevention programs with the scenario which included an oral glucose tolerance test (OGTT). METHODS: We included 4864 participants of the Australian Diabetes, Obesity and Lifestyle study who were aged ≥40 years, did not have known diabetes at baseline, and attended the five year follow-up. The proportions of participants eligible or ineligible for diabetes prevention program were estimated for each scenario. The costs of screening and diabetes prevention programs were also estimated. RESULTS: Screening with OGTT alone identified 21% of participants as eligible for diabetes prevention. While 3.1% of the cohort were identified as high risk and developed diabetes after five years, 1.0% of the cohort were identified as low risk and developed diabetes. The population prevention potential (i.e. sensitivity) for OGTT alone was 76.5%. Screening all Australian adults aged ≥40 years in 2015 by OGTT would have cost a total of AU$2025 million (AU$1031 million on screening and AU$994 million on prevention programs). The total costs of screening and prevention were substantially lower when AUSDRISK was used alone or in combination with a blood test. However, the population prevention potentials were also lower (ranged from 20.1% to 50.7%). CONCLUSIONS: A blood test post non-invasive risk assessment is a worthwhile step in the process of enrolling participants in a diabetes prevention program. Nevertheless, there will be ineligible individuals who proceed to diabetes.

Evaluation of AUSDRISK as a screening tool for lifestyle modification programs: international implications for policy and cost-effectiveness.

OBJECTIVE: To evaluate the current use of Australian Type 2 Diabetes Risk Assessment Tool (AUSDRISK) as a screening tool to identify individuals at high risk of developing type 2 diabetes for entry into lifestyle modification programs. RESEARCH DESIGN AND METHODS: AUSDRISK scores were calculated from participants aged 40-74 years in the Greater Green Triangle Risk Factor Study, a cross-sectional population survey in 3 regions of Southwest Victoria, Australia, 2004-2006. Biomedical profiles of AUSDRISK risk categories were determined along with estimates of the Victorian population included at various cut-off scores. Sensitivity, specificity, positive predictive value (PPV), negative predictive value, and receiver operating characteristics were calculated for AUSDRISK in determining fasting plasma glucose (FPG) ≥6.1 mmol/L. RESULTS: Increasing AUSDRISK scores were associated with an increase in weight, body mass index, FPG, and metabolic syndrome. Increasing the minimum cut-off score also increased the proportion of individuals who were obese and centrally obese, had impaired fasting glucose (IFG) and metabolic syndrome. An AUSDRISK score of ≥12 was estimated to include 39.5% of the Victorian population aged 40-74 (916 000), while a score of ≥20 would include only 5.2% of the same population (120 000). At AUSDRISK≥20, the PPV for detecting FPG≥6.1 mmol/L was 28.4%. CONCLUSIONS: AUSDRISK is powered to predict those with IFG and undiagnosed type 2 diabetes, but its effectiveness as the sole determinant for entry into a lifestyle modification program is questionable given the large proportion of the population screened-in using the current minimum cut-off of ≥12. AUSDRISK should be used in conjunction with oral glucose tolerance testing, fasting glucose, or glycated hemoglobin to identify those individuals at highest risk of progression to type 2 diabetes, who should be the primary targets for lifestyle modification.

Abortive keratoacanthoma: a hitherto unrecognised variant.

AIMS: To study the histological features of abortive keratoacanthoma, a variant that has only recently been recognised. METHODS: A key word search of the database of our pathology practice was carried out for all keratoacanthomas (KAs) reported by one author (DW) over a 14-month period. These cases were then sorted into histological subtypes by age in decades. RESULTS: A total of 3465 cases of KA were reported over this period, of which 582 (16.8%) were of the so-called abortive type. Abortive KAs are characterised by rapid growth and subsequent lichenoid regression at an early stage in their evolution. Lichenoid changes extend for a variable distance beyond the lesion. CONCLUSIONS: Abortive KA is a hitherto unrecognised variant of KA which may be misdiagnosed as squamous cell carcinoma despite its distinctive features. Lichenoid regression, rather than terminal differentiation, is the main mechanism of its involution.

Squamous cell carcinoma arising in keratoacanthoma: a neglected phenomenon in the elderly.

Keratoacanthoma is a unique clinicopathologic entity with a behavior and clinical outcome that differs markedly from that of squamous cell carcinoma. The development of squamous cell carcinoma in a keratoacanthoma alluded to by Rook and Whimster in 1979 and by Reed in 1993 was confirmed by Sánchez Yus et al in 2000. We found this phenomenon in 5.7% of keratoacanthomas in a series of 3465 cases. Its incidence in patients older than 90 years was 13.9%. The incidence of perineural invasion in this series of keratoacanthomas was 0.2%.

A two-dimensional DNA array: the three-layer logpile.

We describe the three-layer logpile (3LL), a two-dimensional DNA array which self-assembles from four synthetic oligonucleotides via a four-armed Holliday junction motif. It consists of three layers of helices, each running at 60 degrees to the others. DNA arrays can be used as periodic templates to create, for example, synthetic protein crystals: this array is designed to maximize structural order by ensuring that helices run continuously, without bending, through the structure. UV absorbance measurements show a rate-dependent hysteresis associated with the assembly of the 3LL. Negative-stain transmission electron microscopy (TEM) of 3LL samples shows that the arrays form extensive sheets (approximately microm(2)) and a process of iterative correlation mapping and averaging of small subsets of digitized TEM micrographs yields an averaged projection image that is consistent with a computer-generated model of the crystal.

A facile method for reversibly linking a recombinant protein to DNA.

We present a facile method for linking recombinant proteins to DNA. It is based on the nickel-mediated interaction between a hexahistidine tag (His(6)-tag) and DNA functionalized with three nitrilotriacetic acid (NTA) groups. The resulting DNA-protein linkage is site-specific. It can be broken quickly and controllably by the addition of a chelating agent that binds nickel. We have used this new linker to bind proteins to a variety of DNA motifs commonly used in the fabrication of nanostructures by DNA self-assembly.

Self-assembly of chiral DNA nanotubes.

A system of DNA "tiles" that is designed to assemble to form two-dimensional arrays is observed to form narrow ribbons several micrometers in length. The uniform width of the ribbons and lack of frayed edges lead us to propose that they are arrays that have curled and closed on themselves to form tubes. This proposal is confirmed by the observation of tubes with helical order.

Phospholipid complexation and association with apolipoprotein C-II: insights from mass spectrometry.

The interactions between phospholipid molecules in suspensions have been studied by using mass spectrometry. Electrospray mass spectra of homogeneous preparations formed from three different phospholipid molecules demonstrate that under certain conditions interactions between 90 and 100 lipid molecules can be preserved. In the presence of apolipoprotein C-II, a phospholipid binding protein, a series of lipid molecules and the protein were observed in complexes. The specificity of binding was demonstrated by proteolysis; the resulting mass spectra reveal lipid-bound peptides that encompass the proposed lipid-binding domain. The mass spectra of heterogeneous suspensions and their complexes with apolipoprotein C-II demonstrate that the protein binds simultaneously to two different phospholipids. Moreover, when apolipoprotein C-II is added to lipid suspensions formed with local concentrations of the same lipid molecule, the protein is capable of remodeling the distribution to form one that is closer to a statistical arrangement. These observations demonstrate a capacity for apolipoprotein C-II to change the topology of the phospholipid surface. More generally, these results highlight the fact that mass spectrometry can be used to probe lipid interactions in both homogeneous and heterogeneous suspensions and demonstrate reorganization of the distribution of lipids upon surface binding of apolipoprotein C-II.